In 1990, the estimated number of new cases of tuberculosis world-wide was 8 million with 2.9 million deaths. Technologic advances that would have greatest impact on the control of tuberculosis would be improved vaccines and improved means of diagnosis of individuals infected with Mycobacterium tuberculosis, particularly those at high risk of progressing to disease.To this point, the major antigens of M. tuberculosis that stimulate protective (and immunopathologic) immune responses and delayed type hypersensitivity are unknown.The goal of AI24298 is to identify targets of the human T-cell response to M. tuberculosis. An unexpected heterogeneity has been demonstrated in the immune response of healthy M. tuberculosis-infected individuals suggesting that protective immunity and DTH may be the aggregate of responses to a number of different antigens rather than the response to one or a few antigens. Of the molecularly-defined antigens, the 30-kDa antigen is a major T-cell stimulus in healthy tuberculin- positive donors. It is of substantial interest, therefore, that patients with pulmonary tuberculosis fail to respond to this antigen. It is possible that this lack of response is a marker of susceptibility to infection, or that the 30-kDa antigen activates antigen-specific immunosuppressive mechanisms. In terms of more completely defining the repertoire of antigens that stimulate human T-cells, methods have been developed and successfully piloted for screening recombinant cosmid expression libraries of mycobacteria as well as culture filtrates of M. tuberculosis.
